(1) Field of the Invention
The present invention relates to a novel anthracycline glycoside and a process for the production of the related compounds.
More particularly, the present invention relates to a novel anthracycline glycoside, 2-hydroxyaclacinomycin B of the general formula ##STR1## and to a process for the production of 2-hydroxyaclacinomycins A, B, and N by fermentation.
(2) Description of the Prior Art
A number of anthracycline glycosides have been found in the culture medium of Streptomyces, and are described in prior literatures. Among them, daunomycin and adriamycin have already been clinically applied for human cancers.
Rhodomycinones, iso-rhodomycinones and rhodomycin-related antibiotics are described in Chem. Ber. 88, 1792-1818 (1955); Chem. Ber. 101, 1341-1348 (1968); J. Med. Chem., 20, 957-960 (1977); Pharmazie 27, 782-789 (1972); Zeit. Allg. Mikrobiol., 14, 551-558 (1974); Tetrahed. Lett. No. 38, 3699-3702 (1973); Folia Microbiol., 24, 293-295 (1979); and J. Antibiotics, 32, 420-424 (1979).
Aclacinomycin A is disclosed in U.S. Pat. No. 3,988,315 and by Oki et al. in J. Antibiotics 28, 830 (1975) and 32, 791-812 (1979).
Cinerubins A and B are disclosed in U.K. Pat. No. 846,130, U.S. Pat. No. 3,864,480, Keller-Schierlein et al., "Antimicrobial Agents and Chemotherapy", page 68 (1970), Chemical Abstracts 54, 1466i (1960) and J. Antibiotics 28, 830 (1975).
2-Hydroxyaclacinomycin A is disclosed in European Patent Application Publication No. 30255.
Further illustrative and summary disclosures of anthracycline antibiotics can be located in Index of Antibiotics from Actinomycetes, Hamao Umezawa, Editor-in-Chief, University Park Press, State college, Pennsylvania, U.S.A. (1967) as follows:
______________________________________ Antibiotics Page numbers ______________________________________ Aclacinomycins A and B 101-102 Adriamycin 122 Carminomycin I 225 Galirubins A - D 405-408 Rhodomycins X - Y 879-880 .beta.-Rhodomycins 881-885 .gamma.-Rhodomycins 886-892 Steffimycin 945 ______________________________________
The textbooks, Antibiotics, Volume 1, Mechanisms of Action, edited by David Gottlieb and Paul D. Shaw, Springer-Verlag New York, Inc., N.Y. (1967) at pages 190-210 contains a review by A. DiMarco entitled "Daunomycin and Related Antibiotics".
Information Bulletin, No. 10, International Center of Information of Antibiotics, in collaboration with WHO, December, 1972, Belgium, reviews anthracyclines and their derivatives.